Anti-inflammatory treatment and risk for depression after first-time stroke in a cohort of 147 487 Danish patients

Anti-inflammatory treatment and risk for depression after first-time stroke in a cohort of 147 487 Danish patients

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J Psychiatry Neurosci 2017;42(5):320-330

Ida Kim Wium-Andersen, MD; Marie Kim Wium-Andersen, MD, PhD; Martin Balslev Jørgensen, MD; Merete Osler, MD


Background: Depression is a common complication after stroke, and inflammation may be a pathophysiological mechanism. This study examines whether anti-inflammatory treatment with acetylsalicylic acid (ASA), nonsteroid anti-inflammatory drugs (NSAIDs) or statins influence the risk of depression after stroke.

Methods: A register-based cohort including all patients admitted to hospital with a first-time stroke from Jan. 1, 2001, through Dec. 31, 2011, and a nonstroke population with a similar age and sex distribution was followed for depression until Dec. 31, 2014. Depression was defined as having a hospital contact with depression or having filled prescriptions for antidepressant medication. The associations between redeemed prescriptions of ASA, NSAIDs or statins with early- (≤ 1 year after stroke or study entry) and late-onset (> 1 year after stroke or study entry) depression were analyzed using Cox proportional hazard regression.

Results: We identified 147 487 patients with first-time stroke and 160 235 individuals without stroke for inclusion in our study. Redeemed prescriptions of ASA, NSAIDs or statins after stroke decreased the risk for early-onset depression, especially in patients with ischemic or severe stroke. Patients who received a combination of anti-inflammatory treatments had the lowest risk for early-onset depression. On the other hand, use of ASA or NSAIDs 1 year after stroke increased the risk for late-onset depression, whereas statin use was associated with a tendency toward a decreased risk.

Limitations: The study used prescription of antidepressant medication as a proxy measure for depression and did not include anti-inflammatory drugs bought over the counter.

Conclusion: Anti-inflammatory treatment is associated with a lower risk for depression shortly after stroke but a higher risk for late depression. This suggests that inflammation contributes differently to the development of depression after stroke depending on the time of onset.

Submitted Dec. 20, 2016; Revised Mar. 15, 2017; Accepted Apr. 6, 2017; Early-released June 20, 2017

Affiliations: From the Psychiatric Center Ballerup, Ballerup, Denmark (I. Wium-Andersen); the Research Center for Prevention and Health, Glostrup Hospital, Glostrup, Denmark (I. Wium-Andersen, M. Wium-Andersen, Osler); the Psychiatric Center Frederiksberg, Frederiksberg, Denmark (M. Wium-Andersen); the Psychiatric Center Copenhagen, Department O, and Institute of Clinical medicine University of Copenhagen, Denmark (I. Wium-Andersen, K. Wium-Andersen, Jørgensen); and the Department of Public Health, Section of Social Medicine, University of Copenhagen, Denmark (Osler).

Funding: The work was supported by the Danish Tryg Foundation [Idn106450] and the Danish Heart Association (Bnr:14-R97-A5003-22834). The sponsors had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript.

Competing interests: None declared.

Contributors: All authors designed the study. M. Osler acquired the data, which all authors analyzed. I. Wium-Andersen and M. Wium-Andersen wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.160244

Correspondence to: Ida Kim Wium-Andersen, Psychiatric Center Ballerup, Maglevænget 2, 2750 Ballerup, Denmark;